Dataset Information

A multifunctional biodegradable brush polymer-drug conjugate for paclitaxel/gemcitabine co-delivery and tumor imaging.

ABSTRACT: A multifunctional biodegradable brush polymer-drug conjugate (BPDC) is developed for the co-delivery of hydrophobic paclitaxel (PTX) and hydrophilic gemcitabine (GEM) chemotherapeutics, as well as a tumor imaging agent. A novel ternary copolymer of conventional, acetylenyl-functionalized and allyl-functionalized lactides is prepared to serve as the backbone precursor of BPDC. Acetylenyl groups of the copolymer are then reacted with poly(ethylene glycol) (PEG) side chains and cyanine5.5, a fluorescent probe, via azide-alkyne click reactions. Subsequently, the allyl groups of the yielded PEG-grafted brush polymer are used to covalently link PTX and GEM onto the backbone via thiol-ene click reactions. The resulting BPDC exhibits an average hydrodynamic diameter of 111 nm. Sustained and simultaneous release of PTX and GEM from the BPDC is observed in phosphate buffered saline, with the release of PTX showing sensitivity in mild acidic conditions. In vitro studies using MIA PaCa-2 human pancreatic cancer cells illustrate the cellular uptake and cytotoxicity of the BPDC. In vivo, the BPDC possesses long blood circulation, tumor accumulation, and enables optical tumor imaging. Further development and testing is warranted for multifunctional conjugated brush polymer systems that integrate combination chemotherapies and imaging.

SUBMITTER: Sun H

PROVIDER: S-EPMC7451085 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A multifunctional biodegradable brush polymer-drug conjugate for paclitaxel/gemcitabine co-delivery and tumor imaging.

Sun Haotian H Yan Lingyue L Chang Michael Yu Zarng MYZ Carter Kevin A KA Zhang Runsheng R Slyker Leigh L Lovell Jonathan F JF Wu Yun Y Cheng Chong C

Nanoscale advances 20190527 7

A multifunctional biodegradable brush polymer-drug conjugate (BPDC) is developed for the co-delivery of hydrophobic paclitaxel (PTX) and hydrophilic gemcitabine (GEM) chemotherapeutics, as well as a tumor imaging agent. A novel ternary copolymer of conventional, acetylenyl-functionalized and allyl-functionalized lactides is prepared to serve as the backbone precursor of BPDC. Acetylenyl groups of the copolymer are then reacted with poly(ethylene glycol) (PEG) side chains and cyanine5.5, a fluore ...[more]

PMID: 32864564

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Project description:A fully biodegradable zwitterionic polymer and the corresponding conjugate with paclitaxel (PTX) were synthesized as promising biomaterials. Allyl-functionalized polylactide (PLA) was employed as the precursor of polymer backbones. UV-induced thiol-ene reaction was conducted to conjugate thiol-functionalized sulfobetaine (SB) with the PLA-based backbone. The resulting zwitterionic polymer did not exhibit considerable cytotoxicity. A polymer-drug conjugate was also obtained by thiol-ene reaction of both thiol-functionalized SB and PTX with allyl-functionalized PLA. The conjugate could readily form narrowly-dispersed nanoparticles in aqueous solutions with a volume-average hydrodynamic diameter (Dh,V) of 19.3 ± 0.2 nm. Such a polymer-drug conjugate-based drug delivery system showed full degradability, well-suppressed non-specific interaction with biomolecules, and sustained drug release. In vitro assessments also confirmed the significant anti-cancer efficacy of the conjugate. After 72 h incubation with PLA-SB/PTX containing 10 µg/mL of PTX, the cell viabilities of A549, MCF7, and PaCa-2 cells were as low as 20.0 ± 2.5%, 1.7 ± 1.7%, and 14.8 ± 0.9%, respectively. Both flow cytometry and confocal microscopy suggested that the conjugates could be easily uptaken by A549 cells before the major release of PTX moieties. Overall, this work elucidates promising potentials of biodegradable zwitterionic polymer-based materials in biomedical applications.Statement of significanceThe applicability of FDA-approved biodegradable aliphatic polyesters has been significantly restricted because they are hydrophobic and lack functionalities. Recently zwitterionic polymers have emerged as promising hydrophilic biomaterials, but most of the reported zwitterionic polymers are non-biodegradable. This study reports a novel aliphatic polyester-based zwitterionic polymer and the corresponding polymer-drug conjugate. Their aliphatic polyester and zwitterionic components provide them with high enzymatic degradability and low nonspecific interactions with biomolecules, respectively. While the zwitterionic polymer did not show noticeable cytotoxicity, the corresponding polymer-anticancer drug conjugate exhibited acid-sensitive sustained drug release, remarkable effectiveness in killing cancer cells, as well as the ready cellular internalization. This work lays a foundation for the further development of synthetic biodegradable zwitterionic polymer-based materials which potentially may have broad and significant biomedical applications.

Dataset Information

A multifunctional biodegradable brush polymer-drug conjugate for paclitaxel/gemcitabine co-delivery and tumor imaging.

Publications

A multifunctional biodegradable brush polymer-drug conjugate for paclitaxel/gemcitabine co-delivery and tumor imaging.

Similar Datasets

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